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A methodology for the development of a finite element numerical model of the tympanic membrane (TM) based on experiments carried out in the time domain on a cadaveric human temporal bone is presented. Using a high-speed digital holographic (HDH) system, acoustically-induced transient displacements of the TM surface are obtained. The procedure is capable to generate and validate the finite element model of the TM by numerical and experimental data correlation. Reverse engineering approach is used to identify key material parameters that define the mechanical response of the TM. Finally, modal numerical simulations of the specimen are performed. Results show the feasibility of the methodology to obtain an accurate model of a specific specimen and to help interpret its behaviour with additional numerical simulations. STATEMENT OF SIGNIFICANCE: Improving knowledge of the dynamic behavior of the tympanic membrane is key to understanding the sound transmission system in human hearing and advance in the treatment of its pathologies. Recently we acquired a new tool to carry out experiments in transient regime by means of digital laser holography, capable of providing a large amount of information in a controlled transient test. In this work, these data are used to develop a methodology that generates a numerical model of the tympanic membrane based on numerical-experimental correlations. It is important to be able to develop models that fit specific patients. In this work, additional modal simulations are also presented that, in addition to validating the results, provide more information on the specimen., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Immunoglobulin A (IgA) nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and it is characterized by mesangial IgA deposition. Asymptomatic hematuria with various degrees of proteinuria is the most common clinical presentation and up to 20%-40% of patients develop end-stage kidney disease within 20 years after disease onset. The pathogenesis of IgAN involves four sequential processes known as the "four-hit hypothesis" which starts with the production of a galactose-deficient IgA1 (gd-IgA1), followed by the formation of anti-gd-IgA1 IgG or IgA1 autoantibodies and immune complexes that ultimately deposit in the glomerular mesangium, leading to inflammation and injury. Although several key questions about the production of gd-IgA1 and the formation of anti-gd-IgA1 antibodies remain unanswered, a growing body of evidence is shedding light on the innate and adaptive immune mechanisms involved in this complex pathogenic process. Herein, we will focus on these mechanisms that, along with genetic and environmental factors, are thought to play a key role in disease pathogenesis., Competing Interests: Paolo Cravedi is an advisor for Chinook Therapeutics and Calliditas Therapeutics. The other authors have no conflict of interest to declare., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Background: Irrigation is commonly used as an adjuvant treatment during the intralesional curettage of bone tumors. The goal of the present study was to analyze the in vitro cytotoxicity of commonly used irrigation solutions on chondrosarcoma and giant cell tumor (GCT) cells as there is no consensus on which solution leads to the greatest amount of cell death., Methods: An in vitro evaluation was performed by exposing human GCT and human chondrosarcoma cell lines to 0.9% saline solution, sterile water, 70% ethanol, 3% hydrogen peroxide, 0.05% chlorhexidine gluconate (CHG), and 0.3% povidone iodine solutions independently for 2 and 5 minutes. A low-cytotoxicity control (LCC) and a high-cytotoxicity control (HCC) were established to determine the mean cytotoxicity of each solution and each solution's superiority to LCC and non-inferiority to HCC., Results: The present study demonstrated that 0.05% CHG was non-inferior to the HCC when chondrosarcoma was exposed for 5 minutes and when GCT was exposed for 2 and 5 minutes (mean cytotoxicity, 99% to 102%) (p < 0.003 for all). Sterile water was superior to the LCC when chondrosarcoma was exposed for 5 minutes and when GCT was exposed for 2 minutes (mean, 28% to 37%) (p < 0.05). Sterile water (mean, 18% to 38%) (p < 0.012) and 3% hydrogen peroxide (mean, 7% to 16%) (p < 0.001) were both inferior to the HCC. The 3 other solutions were non-superior to the LCC (mean, -24% to -5%) (p < 0.023)., Conclusions: In vitro irrigation in 0.05% CHG provided high cytotoxicity, comparable with the HCC. Therefore, the use of a 0.05% CHG solution clinically could serve as a potential chemical adjuvant during intralesional curettage of chondrosarcoma and GCT., Clinical Relevance: In an effort to reduce the burden of residual tumor cells, irrigation solutions are often utilized as adjuvant local therapy. Use of a 0.05% CHG solution clinically could serve as a potential chemical adjuvant to intralesional curettage of chondrosarcoma and GCT. Further in vivo studies may be indicated to assess clinical outcomes and safety associated with the use of 0.05% CHG in the treatment of chondrosarcoma and GCT., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H220 )., (Copyright © 2022 by The Journal of Bone and Joint Surgery, Incorporated.)

Objective: To assess the characteristics, self-reported tobacco use, knowledge, and perceptions about smoking cessation among cancer care providers (CCPs), as well as perceived barriers to inform interventions that can potentially improve quitting rates and the prognosis of cancer patients in Latin America., Methods: A cross-sectional study was conducted among 996 CCPs in six cancer institutions located in Argentina, Brazil, Colombia, Mexico, and Peru. An online survey consisting of 28 close-ended questions adapted from the 2012 International Association for the Study of Lung Cancer survey and the Global Adult Tobacco Survey was administered., Results: The majority of CCPs, ranging from 86.1% in Mexico to 95.9% in Brazil, agreed or strongly agreed that smoking cessation should be integrated into cancer treatment. However, inadequate training on smoking cessation was reported by 66.9%, 69.4%, 70.4%, 72.9%, 85.8%, and 86.4% in Mexico, Colombia (Floridablanca), Argentina, Peru, Brazil, and Colombia (Medellín), respectively, and this difference was statistically significant ( p < 0.001). Moreover, current cigarette smoking prevalence among CCPs was 2.5% in Brazil, 4.6% in Peru, 6.3% in Colombia (Floridablanca), 10.4% in Colombia (Medellín), 11.5% in Mexico, and 15.1% in Argentina, showing a statistically significant difference ( p < 0.001)., Conclusions: Efforts in Latin America should be geared toward assisting CCPs with their quitting efforts and training in smoking cessation practices aimed at achieving a better prognosis and improving cancer patients' quality of life.

Point-of-Care Ultrasonography (PoCUS) aims to include a fifth pillar (insonation) in the classical physical examination in order to obtain images to answer specific questions by the clinician at the patient's bedside, allowing rapid identification of structural or functional abnormalities, enabling more accurate volume assessment and supporting diagnosis, as well as guiding procedures. In recent years, PoCUS has started becoming a valuable tool in day-to-day clinical practice, adopted by healthcare professionals from various medical specialties, never replacing physical examination but improving patient and medical care and experience. Renal patients represent a wide range of diseases, which lends PoCUS a special role as a valuable tool in different scenarios, not only for volume-related information but also for the assessment of a wide range of acute and chronic conditions, enhancing the sensitivity of conventional physical examination in nephrology. PoCUS in the hands of a nephrologist is a precision medicine tool., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Depression and suicidal behavior are interrelated, stress-associated mental health conditions, each lacking biological verifiability. Concepts of predictive, preventive, and personalized medicine (3PM) are almost completely missing for both conditions but are of utmost importance. Prior research reported altered levels of the stress hormone cortisol in the scalp hair of depressed individuals, however, data on hair cortisol levels (HCL) for suicide completers (SC) are missing. Here, we aimed to identify differences in HCL between subject with depression ( n = 20), SC ( n = 45) and mentally stable control subjects ( n = 12) to establish the usage of HCL as a new target for 3PM. HCL was measured in extracts of pulverized hair (1-cm and 3-cm hair segments) using ELISA. In 3-cm hair segments, an average increase in HCL for depressed patients (1.66 times higher; p  = .011) and SC (5.46 times higher; p  = 1.65 × 10 -5 ) compared to that for controls was observed. Furthermore, the average HCL in SC was significantly increased compared to that in the depressed group (3.28 times higher; p  = 1.4 × 10 -5 ). A significant correlation between HCL in the 1-cm and the 3-cm hair segments, as well as a significant association between the severity of depressive symptoms and HCL (3-cm segment) was found. To conclude, findings of increased HCL in subjects with depression compared to that in controls were replicated and an additional increase in HCL was seen in SC in comparison to patients with depression. The usage of HCL for creating effective patient stratification and predictive approach followed by the targeted prevention and personalization of medical services needs to be validated in follow-up studies., Competing Interests: Competing interestsThe authors have no relevant financial or non-financial interests to disclose. AK is an editorial board member of the journal, but had no involvement in, influence over, or access to the details of the peer review process of this work., (© The Author(s) 2022.)

Background: The variation of plasma d-dimer, an inflammatory marker, from pre-explantation to pre-reimplantation in two-stage revision remains unclear. Our objective was to evaluate delta-changes (Δ) in d-dimer, erythrocyte sedimentation rate (ESR), and C-reactive-protein (CRP), to ascertain whether these delta-changes are associated with the outcome of reimplantation. We hypothesized a decrease in d-dimer before reimplantation., Methods: A retrospective review was performed on a consecutive series of 95 two-stage revisions indicated for periprosthetic joint infection. Surgeries were performed by 3 surgeons at a single institution (2018-2020). The minimum follow-up was 1 year. The inclusion criteria comprised availability of d-dimer results at pre-explantation and pre-reimplantation. As a result, only 30 reimplantations were included. Success of reimplantation was defined by Musculoskeletal Infection Society outcome reporting tool: Tier 1/Tier 2 vs Tier 3/Tier 4. Nonparametric tests and Mann-Whitney U-tests were conducted to compare Δd-dimer% (pre-explantation value - pre-reimplantation value/pre-explantation value × 100). The bootstrapped receiver operating characteristic curve analyses with 2,000 replicates of 30 cases were conducted., Results: The median time between explantation and reimplantation was 86 days (interquartile range [IQR] = 77.7-138.5 days). Overall, a paradoxical median percent increase (Δd-Dimer% [INCREMENT] = 12.6%) in d-dimer was found from pre-explantation to pre-reimplantation (IQR = -28.06% to 77.3%). However, there was a percentage decrease in ESR (ΔESR% [DECREMENT] = -40%; IQR = -70.52% to 3.85%) and CRP (ΔCRP% [DECREMENT] = -75%; IQR = -87.43% to -61.34%). The changes in all these markers were not different between Musculoskeletal Infection Society Tier 1/2 and 3/4 outcomes (Δd-Dimer%, P = .146; ΔESR%, P = .946; ΔCRP%, P = .463). With area under curve of 0.676, Δd-dimer% (INCREMENT) appeared to be performing best in diagnosing infection control, which was nonexplanatory., Conclusion: Plasma d-dimer paradoxically increases before reimplantation while other inflammatory markers (ESR/CRP) decrease, emphasizing that surgeons shall adopt caution using d-dimer to make clinical decisions., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The SuperCam instrument, onboard the Perseverance rover (Mars 2020 mission) is designed to perform remote analysis on the Martian surface employing several spectroscopic techniques such as Laser Induced Breakdown Spectroscopy (LIBS), Time-Resolved Raman (TRR), Time-Resolved Fluorescence (TRF) and Visible and Infrared (VISIR) reflectance. In addition, SuperCam also acquires high-resolution images using a color remote micro-imager (RMI) as well as sounds with its microphone. SuperCam has three main subsystems, the Mast Unit (MU) where the laser for chemical analysis and collection optics are housed, the Body Unit (BU) where the different spectrometers are located inside the rover, and the SuperCam Calibration Target (SCCT) located on the rover's deck to facilitate calibration tests at similar ambient conditions as the analyzed samples. To perform adequate calibrations on Mars, the 22 mineral samples included in the complex SCCT assembly must have a very homogeneous distribution of major and minor elements. The analysis and verification of such homogeneity for the 5-6 replicates of the samples included in the SCCT has been the aim of this work. To verify the physic-chemical homogeneity of the calibration targets, micro Energy Dispersive X-ray Fluorescence (EDXRF) imaging was first used on the whole surface of the targets, then the relative abundances of the detected elements were computed on 20 randomly distributed areas of 100 × 100 μm. For those targets showing a positive Raman response, micro-Raman spectroscopy imaging was performed on the whole surface of the targets at a resolution of 100 × 100 μm. The %RSD values (percent of relative standard deviation of mean values) for the major elements measured with EDXRF were compared with similar values obtained by two independent LIBS set-ups at spot sizes of 300 μm in diameter. The statistical analysis showed which elements were homogeneously distributed in the 22 mineral targets of the SCCT, providing their uncertainty values for further calibration. Moreover, nine of the 22 targets showed a good Raman response and their mineral distributions were also studied. Those targets can be also used for calibration purposes of the Raman part of SuperCam using the wavenumbers of their main Raman bands proposed in this work., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Cement restrictors (CRs) are devices that allow occlusion of the femoral canal in order to obtain greater interdigitation of the cement between the bone and a better pressurization, which generates an increase in the survival of cemented stems. The aim of this study was to evaluate the efficacy of the different CRs used and propose a classification of this device., Materials and Methods: An experimental study was carried out, where 7 CR references of different designs and manufacturers were taken. Later, tests were carried out on 9 chlorinated polyvinyl chloride tubes for each reference, to achieve a total of 63 tests., Results: In our study, 34.9% of the CRs in ultra high molecular weight polyethylene failed, presenting migration and allowing cement to leak while none of the gelatin RC failed., Conclusion: The RC with an umbrella design proved to be the less effective, presented a higher incidence of migration and cement leakage, while the gelatin CRs were the best performers. Based on the results of this study, an analysis of the CR design was carried out and a classification was proposed that divides these devices into 2 types., (Copyright © 2021 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.)

A new, non-destructive methodology is proposed in this work in order to determine the mechanical properties of membrane using vibro-acoustic tests. This procedure is based on the dynamic analysis of the behavior of the membrane. When the membrane is subjected to a sound excitation it responds by vibrating based on its modal characteristics and this modal parameter is directly related to its mechanical properties. The paper is structured in two parts. First, the theoretical bases of the test are presented. The interaction between the sound waves and the membrane (mechano-acoustic coupling) is complex and requires meticulous study. It was broadly studied by means of numerical simulations. A summary of this study is shown. Aspects, such as the position of the sound source, the measuring points, the dimensions of the membrane, the frequency range, and the magnitudes to be measured, among others, were evaluated. The validity of modal analysis curve-fitting techniques to extract the modal parameter from the data measures was also explored. In the second part, an experimental test was performed to evaluate the validity of the method. A membrane of the same material with three different diameters was measured with the aim of estimating the value of the Young's modulus. The procedure was applied and satisfactory results were obtained. Additionally, the experiment shed light on aspects that must be taken account in future experiments.

»: As the number of primary total joint arthroplasty (TJA) procedures continues to rise, megaprostheses have found an emerging role in more complex revision arthroplasty cases that require additional reconstruction, stability, and restoration of function., »: Megaprosthesis options have evolved: in addition to cemented prostheses, cementless and even hybrid fixation designs optimize longevity. Proximal femoral replacement (PFR), distal femoral replacement (DFR), proximal tibial replacement (PTR), and total femoral replacement (TFR) are all limb salvage options in the setting of substantial bone loss, poor bone quality, and soft-tissue compromise., »: Dislocation is one of the most common complications after PFR, likely due to the loss of soft-tissue integrity, most notably the hip abductor musculature from the greater trochanter. The utilization of dual-mobility constructs, larger femoral heads, elevated acetabular liners, and constrained acetabular liners may reduce the risk of instability and improve overall hip function., »: Patients with megaprostheses may be more prone to periprosthetic joint infection and surgical site infection given multiple variables, such as the lengthy nature of the surgical procedure, prolonged wound exposure, extensive soft-tissue dissection and resection, poor soft-tissue coverage, and poorer host status., »: Despite advances in technology, complication and revision rates remain high after megaprosthesis reconstruction. Therefore, thorough attention to patient-specific factors must be considered for appropriate use of these constructs., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSREV/A807)., (Copyright © 2022 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: The acute and long-term effects of severe acute respiratory syndrome coronavirus 2 infection in individuals with GN are still unclear. To address this relevant issue, we created the International Registry of COVID-19 infection in GN., Methods: We collected serial information on kidney-related and -unrelated outcomes from 125 GN patients (63 hospitalized and 62 outpatients) and 83 non-GN hospitalized patients with coronavirus disease 2019 (COVID-19) and a median follow-up period of 6.4 (interquartile range 2.3-9.6) months after diagnosis. We used logistic regression for the analyses of clinical outcomes and linear mixed models for the longitudinal analyses of eGFR. All multiple regression models were adjusted for age, sex, ethnicity, and renin-angiotensin-aldosterone system inhibitor use., Results: After adjustment for pre-COVID-19 eGFR and other confounders, mortality and AKI did not differ between GN patients and controls (adjusted odds ratio for AKI=1.28; 95% confidence interval [CI], 0.46 to 3.60; P =0.64). The main predictor of AKI was pre-COVID-19 eGFR (adjusted odds ratio per 1 SD unit decrease in eGFR=3.04; 95% CI, 1.76 to 5.28; P <0.001). GN patients developing AKI were less likely to recover pre-COVID-19 eGFR compared with controls (adjusted 6-month post-COVID-19 eGFR=0.41; 95% CI, 0.25 to 0.56; times pre-COVID-19 eGFR). Shorter duration of GN diagnosis, higher pre-COVID-19 proteinuria, and diagnosis of focal segmental glomerulosclerosis or minimal change disease were associated with a lower post-COVID-19 eGFR., Conclusions: Pre-COVID-19 eGFR is the main risk factor for AKI regardless of GN diagnosis. However, GN patients are at higher risk of impaired eGFR recovery after COVID-19-associated AKI. These patients (especially those with high baseline proteinuria or a diagnosis of focal segmental glomerulosclerosis or minimal change disease) should be closely monitored not only during the acute phases of COVID-19 but also after its resolution., Competing Interests: O. Bestard reports patents and inventions with Oxford Immunotec and is associate editor of Transplant International and Frontiers in Immunology. A. Bruchfeld reports consultancy agreements with AstraZeneca, Chemocentryx, Fresenius, and Merck; a research grant from AstraZeneca; honoraria from Bayer, Chemocentryx, Fresenius, Merck, and Vifor; and is a member of the ERA-EDTA scientific advisory board 2018–2024, chair of the ERA-EDTA Immunonephrology Working Group, and vice-chair of the Swedish Renal Fund. G. Comai reports honoraria from Alexion, Astellas, and Novartis. P. Cravedi reports honoraria as an advisor for Chinook Therapeutics and is associate editor for the Journal of Nephrology and the American Journal of Transplantation. G. Fernandez Juarez reports research funding from Instituto Salud Calos III and honoraria from Alexion and GSK. E. Fiaccadori is on the editorial board of the Journal of Nephrology and Blood Purification and is a member of the Italian Society of Nephrology and the European Society of Parenteral and Enteral Nutrition. O. Flossmann reports consultancy agreements with Vifor Pharma has other interests/relationships with the British Medical Association, European Vasculitis Society, Renal Association (UK), Royal College of Physicians London, and UK Ireland Vasculitis Society. C. García-Carro reports consultancy agreements with Astellas, AstraZeneca, Boehringer Ingelheim Lilly, Esteve, Novartis and Baxter, Novo Nordisk, and Otsuka; honoraria from Astellas, AstraZeneca, Boehringer Ingelheim Lilly, Esteve, Novartis and Baxter, Novo Nordisk, and Otsuka; and is a scientific advisor for or member of AstraZeneca, Boehringer Ingelheim Lilly, Mundipharma, and Novo Nordisk. M. Griffith reports honoraria from Retrophin’s advisory board. A. J. Hamilton is on the editorial board of the Journal of Kidney Care and is a member of the SONG-Kids Life Participation Expert Working Group. T. Leach reports honoraria from Janssen for conference attendance in 2012 and is a scientific advisor to the National Institute for Health and Care Excellence. L. Lightstone reports consultancy agreements with Achillion, Alexion, AstraZeneca, Aurinia, BMS, GSK, Kezar, Novartis, Pfizer, and Roche; honoraria from Alexion, AstraZeneca, BMS, GSK, and Pfizer; is a scientific advisor or member of EU Exec Lupus Nephritis Trials Network; is on the advisory board of Nature Reviews Nephrology; participates in a speakers’ bureau for Alexion and GSK; is a trustee of Kidney Research UK 2018–2022; is an executive member of the International Society of Nephrology 2021–2023; is deputy chair of Western Regional Board of the International Society of Nephrology; and is a clinical expert representing the Renal Association response to NICE on STA for belimumab in lupus 2020–2021. U. Maggiore reports consultancy agreements with Biotest, Chiesi, GSK, Hansa, Novartis, Sandoz, and Takeda. J. Manrique is a scientific advisor for or member of AstraZeneca, Boehringer, and Viphor Pharma. E. Morales reports consultancy agreements with Alexion, Celgene, Viphor Fresenius, and Vifor Pharma. J.A. Niño-Cruz reports research funding from Pfizer Scientific Institute and participates in a speakers’ bureau for Takeda and Roche. A. Ortiz reports consultancy agreements with Retrophin and Sanofi Genzyme; research funding from AstraZeneca, Mundipharma, and Sanofi Genzyme; honoraria from Advicciene, Alexion, Amgen, Amicus, Astellas, AstraZeneca, Bayer, Chiesi, Fresenius Medical Care, Idorsia, Kyowa Kirin, Menarini, Otsuka, Sanofi Genzyme, and Vifor Fresenius Medical Care Renal Pharma; is a member of the Spanish Society of Nephrology; is editor-in-chief of the Clinical Kidney Journal; is on the editorial boards of the Journal of Nephrology, Journal of the American Society of Nephrology, and Peritoneal Dialysis International; is a member of SOMANE and ERA Councils; is on the board of directors for IIS-Fundacion Jimenez Diaz UAM; is on the scientific advisory board of the Dutch Kidney Foundation; honoraria listed above are for speaker engagements: Advicciene, Alexion, Astellas, AstraZeneca, Amicus, Amgen, Bayer, Chiesi, Fresenius Medical Care, Idorsia, Kyowa Kirin, Menarini, Otsuka, Sanofi Genzyme, and Vifor Fresenius Medical Care Renal Pharma. S. Sinha reports consultancy agreements with Sanifit; research funding from Amgen, AstraZeneca, and Ethicon; and honoraria from AstraZeneca, Bayer, Napp Pharmaceuticals, Novartis, and Sanofi Genzyme. M.F. Slon-Roblero reports consultancy agreements with Baxter, Fresenius, and Nipro; and honoraria from Baxter, Fresenius, and Nipro. M.J. Soler reports consultancy agreements with AstraZeneca, Bayer, Boehringer, Esteve, Jansen, Mundipharma, Novo Nordisk, Travere, and ICU; research funding from Abbvie and Boehringer; honoraria from AstraZeneca, Boehringer, Esteve, FMC, Jansen, ICU Medical, Mundipharma, Novo Nordisk, Otsuka, and Travere; patents and inventions: U691ES00; is a scientific advisor for or member of BMC Nephrology and Clinical Kidney Journal; is a former member of ERA-EDTA Council; participates in a speakers’ bureau for AstraZeneca, Bayer, Boehringer, Esteve, FMC, Jansen, Mundipharma, Novo Nordisk, and Vifor; is a member of the Sociedad Española de Nefrología and Sociedad Catalana de Nefrologia; and is elected editor-in-chief of the Clinical Kidney Journal. All remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

Case: A 76-year-old man presented with metastatic renal cell carcinoma (RCC) in the right acetabulum with pelvic compromise. The patient had right hip pain and difficulty with ambulation, as such he elected to undergo tumor resection with subsequent reconstruction of pelvic defect. Given the size and location of the anticipated pelvic defect, robotic-assisted hip arthroplasty was used to execute prosthetic component placement and anatomic pelvic reconstruction., Conclusion: Advances in technology, such as robotics and 3D navigation, have application in orthopaedic oncology surgery, especially for reconstructions after pelvic resections. The goal of this case report is to describe the utility of this technology in a case of metastatic RCC., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/B724)., (Copyright © 2021 by The Journal of Bone and Joint Surgery, Incorporated.)

BACKGROUND Posterior reversible encephalopathy syndrome (PRES), also known as reversible posterior leukoencephalopathy, is a neurotoxic state with multiple etiologies characterized by altered mental state, headaches, visual abnormalities, and seizures. This clinico-radiological syndrome is rare, and a high index of suspicion is needed to diagnose, provide adequate treatment, and prevent irreversible neurological sequelae. CASE REPORT We present a case of a woman with end-stage renal disease (ESRD) who presented with acute confusion and non-convulsive seizures and was later diagnosed with PRES. In this case, altered mental status was initially thought to be secondary to uremic encephalopathy. A diagnosis of PRES was subsequently made after she had several sessions of HD without significant improvement in her mental state, prompting magnetic resonant imaging (MRI) for further evaluation. Specific risk factors for PRES, including blood pressure fluctuations, were targeted and she made significant clinical recovery but had residual functional impairment. CONCLUSIONS This case underscores the need for a high index of suspicion, especially in cases with atypical presentation, as delayed diagnosis can lead to suboptimal outcomes.

Background: Blood conservation and reduction in the need for allogeneic blood transfusion (ABT) has been a subject of importance in total hip arthroplasty. There are a number of well-recognized parameters that influence blood loss during total hip arthroplasty (THA). The role of surgical approach on blood loss and the rate of ABT during THA is not well studied. The hypothesis of this study was that blood loss and the need for ABT is lower with direct anterior (DA) approach., Methods: In a case-control retrospective cohort study, we analyzed 1,524 primary THAs performed at a single institution by seven fellowship-trained surgeons between January 2015 to March 2017. All patients received THA using either the modified direct lateral (DL) or direct anterior (DA) approach using a standard operating table. The overall ABT rate was 10.2% (155/1,524) in the cohort. Demographic, surgical, and postoperative data were extracted and analyzed. Logistic regression was used to identify independent risk factors for transfusion., Results: Higher preoperative hemoglobin (p<0.001), use of DA approach (p<0.016) and administration of tranexamic acid TXA, (p=0.024) were identified as independent factors which reduced the odds of ABT. Operative time (p<0.001) was associated with an increased odd of ABT, while age, BMI and type of anesthesia were not statistically significant., Conclusion: Based on the findings of this study, direct anterior approach for THA appears to be protective against blood loss and reduced ABT rate, when controlling for confounding variables.

The ability to identify compositional changes in the intestinal microbiota of parasitized hosts is important for understanding the physiological processes that may affect animal productivity. Within the field of host-parasite interactions, many studies have suggested that helminths can influence the microbial composition of their hosts via their immunomodulatory effects. Bovine fascioliasis is a helminthiasis widely studied by immunologists, but with little information available regarding gut microbial communities. Thus, we aimed to describe the composition of the intestinal microbiota of Holstein Fasciola-positive and -negative cattle using parasitological methods and ELISA (enzyme-linked immunosorbent assay). Bovine fecal samples (n = 65) were obtained from livestock slaughter plants in the Cundi-Boyacense Colombian highlands (a hyperendemic region for bovine fascioliasis) and studied by amplicon-based next-generation 16S-rRNA and 18S-rRNA gene sequencing. From these samples, 35 were Fasciola hepatica-negative and, 30 were F. hepatica-positive in our detection analysis. Our results showed a reduction in the relative abundance of Bacteroidetes and Ascomycota in the Fasciola-positive samples, along with decreased relative abundances of the commensal taxa previously associated with fermentation and digestion processes. However, metabolomic approaches and functional analyzes of the intestinal microbiota are necessary to support these hypothesis. These findings are a small first step in the development of research aimed at understanding how microbial populations in bovines are modulated in liver helminth infections., Competing Interests: The authors have declared that no competing interests exist.

Age and chronic kidney disease have been described as mortality risk factors for coronavirus disease 2019 (COVID-19). Currently, an important percentage of patients in haemodialysis are elderly. Herein, we investigated the impact of age on mortality among haemodialysis patients with COVID-19. Data was obtained from the Spanish COVID-19 chronic kidney disease (CKD) Working Group Registry. From 18 March 2020 to 27 August 2020, 930 patients on haemodialysis affected by COVID-19 were included in the Registry. A total of 254 patients were under 65 years old and 676 were 65 years or older (elderly group). Mortality was 25.1% higher (95% CI: 22.2-28.0%) in the elderly as compared to the non-elderly group. Death from COVID-19 was increased 6.2-fold in haemodialysis patients as compared to the mortality in the general population in a similar time frame. In the multivariate Cox regression analysis, age (hazard ratio (HR) 1.59, 95% CI: 1.31-1.93), dyspnea at presentation (HR 1.51, 95% CI: 1.11-2.04), pneumonia (HR 1.74, 95% CI: 1.10-2.73) and admission to hospital (HR 4.00, 95% CI: 1.83-8.70) were identified as independent mortality risk factors in the elderly haemodialysis population. Treatment with glucocorticoids reduced the risk of death (HR 0.68, 95% CI: 0.48-0.96). In conclusion, mortality is dramatically increased in elderly haemodialysis patients with COVID-19. Our results suggest that this high risk population should be prioritized in terms of protection and vaccination.

Background and Aims: Digital tomosynthesis has proven useful in the evaluation of damage to joints. This study aims to describe the most common digital tomosynthesis findings for four rheumatological entities and to compare the usefulness of this technique with that of other imaging techniques., Materials and Methods: Following the PRISMA guidelines, we systematically searched the literature for articles about the use of digital tomosynthesis in rheumatoid arthritis, osteoarthritis, spondyloarthritis, and gout. We used the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) criteria to evaluate the quality of the articles included., Results: We included 13 articles. For rheumatoid arthritis, osteoarthritis, and spondyloarthritis, digital tomosynthesis detected bone abnormalities better than plain-film X-rays; however, for gout, the results were variable., Conclusions: Digital tomosynthesis can play an important role in the evaluation of skeletal abnormalities in rheumatological disease, especially compared to plain-film X-rays., (Copyright © 2020 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.)

The effects of SARS-CoV-2 infection on individuals with immune-mediated glomerulonephritis, who are often undergoing immunosuppressive treatments, are unknown. Therefore, we created the International Registry of COVID infection in glomerulonephritis (IRoc-GN) and identified 40 patients with glomerulonephritis and COVID-19 followed in centers in North America and Europe. Detailed information on glomerulonephritis diagnosis, kidney parameters, and baseline immunosuppression prior to infection were recorded, as well as clinical presentation, laboratory values, treatment, complications, and outcomes of COVID-19. This cohort was compared to 80 COVID-positive control cases from the general population without glomerulonephritis matched for the time of infection. The majority (70%) of the patients with glomerulonephritis and all the controls were hospitalized. Patients with glomerulonephritis had significantly higher mortality (15% vs. 5%, respectively) and acute kidney injury (39% vs. 14%) than controls, while the need for kidney replacement therapy was not statistically different between the two groups. Receiving immunosuppression or renin-angiotensin-aldosterone system inhibitors at presentation did not increase the risk of death or acute kidney injury in the glomerulonephritis cohort. In the cohort with glomerulonephritis, lower serum albumin at presentation and shorter duration of glomerular disease were associated with greater risk of acute kidney injury and need for kidney replacement therapy. No differences in outcomes occurred between patients with primary glomerulonephritis versus glomerulonephritis associated with a systemic autoimmune disease (lupus or vasculitis). Thus, due to the higher mortality and risk of acute kidney injury than in the general population without glomerulonephritis, patients with glomerulonephritis and COVID-19 should be carefully monitored, especially when they present with low serum albumin levels., (Copyright © 2020 International Society of Nephrology. All rights reserved.)

This research presents the results of a pilot system used for water treatment to be supplied to single-family or small housing nucleus at rural sector. The pilot system is constituted by an up-flow aerated filter with ceramic carrier, followed by a second down-flow filter of silica sand. The pilot plant was installed in a rural sector of the province of Loja, Ecuador, with the main purpose of monitoring the reduction in bacteria in the water for human consumption. Two natural clays from the area were tested. They were transformed into sphere-type ceramics, and then, they were placed in the pilot filters. These both natural clays are inorganic materials with high content of aluminosilicate clay minerals with favourable characteristics to achieve greater efficiency for the reduction in bacteria. The acclimatization time of 60 days allowed to achieve optimum treatment efficiency performance until 90 days of operation. The physicochemical parameters, namely temperature, pH, dissolved oxygen and total dissolved solids, were monitored throughout the experiments. Regarding microbiological parameters, up to 99% of total coliforms removal was reached for the clay called CF-CC and 79% for the other, called CF-CV. In addition, 100% of total coliforms and Escherichia Coli removal was reached for both clay systems. Social and economic viability of the proposed treatment is also analysed in the manuscript.

Kidney transplant recipients may be at a high risk of developing critical coronavirus disease 2019 (COVID-19) illness due to chronic immunosuppression and comorbidities. We identified hospitalized adult kidney transplant recipients at 12 transplant centers in the United States, Italy, and Spain who tested positive for COVID-19. Clinical presentation, laboratory values, immunosuppression, and treatment strategies were reviewed, and predictors of poor clinical outcomes were determined through multivariable analyses. Among 9845 kidney transplant recipients across centers, 144 were hospitalized due to COVID-19 during the 9-week study period. Of the 144 patients, 66% were male with a mean age of 60 (±12) years, and 40% were Hispanic and 25% were African American. Prevalent comorbidities included hypertension (95%), diabetes (52%), obesity (49%), and heart (28%) and lung (19%) disease. Therapeutic management included antimetabolite withdrawal (68%), calcineurin inhibitor withdrawal (23%), hydroxychloroquine (71%), antibiotics (74%), tocilizumab (13%), and antivirals (14%). During a median follow-up period of 52 days (IQR: 16-66 days), acute kidney injury occurred in 52% cases, with respiratory failure requiring intubation in 29%, and the mortality rate was 32%. The 46 patients who died were older, had lower lymphocyte counts and estimated glomerular filtration rate levels, and had higher serum lactate dehydrogenase, procalcitonin, and interleukin-6 levels. In sum, hospitalized kidney transplant recipients with COVID-19 have higher rates of acute kidney injury and mortality., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Individuals with kidney failure are at increased risk of cardiovascular events, as well as infections and malignancies, but the associated immunological abnormalities are unclear. We hypothesized that the uremic milieu triggers a chronic inflammatory state that, while accelerating atherosclerosis, promotes T cell exhaustion, impairing effective clearance of pathogens and tumor cells. Clinical and demographic data were collected from 78 patients with chronic kidney disease (CKD) ( n = 42) or end-stage kidney disease (ESKD) ( n = 36) and from 18 healthy controls (HC). Serum cytokines were analyzed by Luminex. Immunophenotype of T cells was performed by flow cytometry on peripheral blood mononuclear cells. ESKD patients had significantly higher serum levels of IFN-γ, TNF-α, sCD40L, GM-CSF, IL-4, IL-8, MCP-1, and MIP-1β than CKD and HC. After mitogen stimulation, both CD4 + and CD8 + T cells in ESKD group demonstrated a pro-inflammatory phenotype with increased IFN-γ and TNF-α, whereas both CKD and ESKD patients had higher IL-2 levels. CKD and ESKD were associated with increased frequency of exhausted CD4 + T cells (CD4 + KLRG1 + PD1 + CD57 - ) and CD8 + T cells (CD8 + KLRG1 + PD1 + CD57 - ), as well as anergic CD4 + T cells (CD4 + KLRG1 - PD1 + CD57 - ) and CD8 + T cells (CD8 + KLRG1 - PD1 + CD57 - ). Although total percentage of follicular helper T cell (T FH ) was similar amongst groups, ESKD had reduced frequency of T FH1 (CCR6 - CXCR3 + CXCR5 + PD1 + CD4 + CD8 - ), but increased T FH2 (CCR6 - CXCR3 - CXCR5 + PD1 + CD4 + CD8 - ), and plasmablasts (CD3 - CD56 - CD19 + CD27 high CD38 high CD138 - ). In conclusion, kidney failure is associated with pro-inflammatory markers, exhausted T cell phenotype, and upregulated T FH2 , especially in ESKD. These immunological changes may account, at least in part, for the increased cardiovascular risk in these patients and their susceptibility to infections and malignancies., (Copyright © 2020 Hartzell, Bin, Cantarelli, Haverly, Manrique, Angeletti, Manna, Murphy, Zhang, Levitsky, Gallon, Yu and Cravedi.)

Kidney glomerulosclerosis commonly progresses to end-stage kidney failure, but pathogenic mechanisms are still poorly understood. Here, we show that podocyte expression of decay-accelerating factor (DAF/CD55), a complement C3 convertase regulator, crucially controls disease in murine models of adriamycin (ADR)-induced focal and segmental glomerulosclerosis (FSGS) and streptozotocin (STZ)-induced diabetic glomerulosclerosis. ADR induces enzymatic cleavage of DAF from podocyte surfaces, leading to complement activation. C3 deficiency or prevention of C3a receptor (C3aR) signaling abrogates disease despite DAF deficiency, confirming complement dependence. Mechanistic studies show that C3a/C3aR ligations on podocytes initiate an autocrine IL-1β/IL-1R1 signaling loop that reduces nephrin expression, causing actin cytoskeleton rearrangement. Uncoupling IL-1β/IL-1R1 signaling prevents disease, providing a causal link. Glomeruli of patients with FSGS lack DAF and stain positive for C3d, and urinary C3a positively correlates with the degree of proteinuria. Together, our data indicate that the development and progression of glomerulosclerosis involve loss of podocyte DAF, triggering local, complement-dependent, IL-1β-induced podocyte injury, potentially identifying new therapeutic targets., Competing Interests: Disclosures: J.M. Thurman reported a patent to US 7,999,082 issued "Alexion Pharmaceuticals, Inc." and a patent to US 8,703,140 B2 issued "Alexion Pharmaceuticals, Inc." J. Manrique reported personal fees from Alexion Pharmaceuticals, Inc. P.S. Heeger reported personal fees from Mallinckrodt Pharmaceuticals during the conduct of the study. No other disclosures were reported., (© 2020 Angeletti et al.)

Background: Acetabular fractures often require surgical intervention for fracture fixation and can result in premature osteoarthritis of the hip joint. This study hypothesized that total hip arthroplasty (THA) in patients with a prior acetabular fracture who had undergone open reduction and internal fixation (ORIF) is associated with a higher rate of subsequent periprosthetic joint infection (PJI)., Methods: About 72 patients with a history of acetabular fracture that required ORIF, undergoing conversion THA between 2000 and 2017 at our institution, were matched based on age, gender, body mass index, Charlson comorbidity index, and date of surgery in a 1:3 ratio with 215 patients receiving primary THA. The mean follow-up for the conversion THA cohort was 2.9 years (range, 1-12.15) and 3.06 years (range, 1-12.96) for the primary THA., Results: Patients with a previous acetabular fracture, compared with the primary THA patients, had longer operative times, greater operative blood loss, and an increased need for allogeneic blood transfusion (26.4% vs 4.7%). Most notably, PJI rate was significantly higher in acetabular fracture group at 6.9% compared with 0.5% in the control group. Complications, such as aseptic revision, venous thromboembolism, and mortality, were similar between both groups., Conclusion: The present study demonstrates that conversion THA in patients with prior ORIF of acetabular fractures is associated with higher complication rate, in particular PJI, and less optimal outcome compared with patients undergoing primary THA. The latter findings compel us to seek and implement specific strategies that aim to reduce the risk of subsequent PJI in these patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Primary membranous nephropathy (MN) is characterized by the presence of antipodocyte antibodies, but studies describing phenotypic and functional abnormalities in circulating lymphocytes are limited., Methods: We analyzed 68 different B- and T-cell subsets using flow cytometry in 30 MN patients (before initiating immunosuppression) compared with 31 patients with non-immune-mediated chronic kidney disease (CKD) and 12 healthy individuals. We also measured 19 serum cytokines in MN patients and in healthy controls. Lastly, we quantified the ex vivo production of phospholipase A2 receptor (PLA2R)-specific IgG by plasmablasts (measuring antibodies in culture supernatants and by the newly developed FluoroSpot assay [AutoImmun Diagnostika, Strasberg, Germany]) and assessed the circulating antibody repertoire by phage immunoprecipitation sequencing (PhIP-Seq)., Results: After adjusting for multiple testing, plasma cells and regulatory B cells (B REG ) were significantly higher ( P  < 0.05) in MN patients compared with both control groups. The percentages of circulating plasma cells correlated with serum anti-PLA2R antibody levels ( P  = 0.042) and were associated with disease activity. Ex vivo -expanded PLA2R-specific IgG-producing plasmablasts generated from circulating PLA2R-specific memory B cells (mBCs) correlated with serum anti-PLA2R IgG antibodies ( P  < 0.001) in MN patients. Tumor necrosis factor-α (TNF-α) was the only significantly increased cytokine in MN patients ( P  < 0.05), whereas there was no significant difference across study groups in the autoantibody and antiviral antibody repertoire., Conclusion: This extensive phenotypic and functional immune characterization shows that autoreactive plasma cells are present in the circulation of MN patients, providing a new therapeutic target and a candidate biomarker of disease activity., (© 2020 International Society of Nephrology. Published by Elsevier Inc.)

Key Points: We confirm that GABA B receptors (GABA B -Rs) are involved in the termination of Up-states; their blockade consistently elongates Up-states. GABA B -Rs also modulate Down-states and the oscillatory cycle, thus having an impact on slow oscillation rhythm and its regularity. The most frequent effect of GABA B -R blockade is elongation of Down-states and subsequent decrease of oscillatory frequency, with an increased regularity. In a quarter of cases, GABA B -R blockade shortened Down-states and increased oscillatory frequency, changes that are independent of firing rates in Up-states. Our computer model provides mechanisms for the experimentally observed dynamics following blockade of GABA B -Rs, for Up/Down durations, oscillatory frequency and regularity. The time course of excitation, inhibition and adaptation can explain the observed dynamics of the network. This study brings novel insights into the role of GABA B -R-mediated slow inhibition on the slow oscillatory activity, which is considered the default activity pattern of the cortical network., Abstract: Slow wave oscillations (SWOs) dominate cortical activity during deep sleep, anaesthesia and in some brain lesions. SWOs are composed of periods of activity (Up states) interspersed with periods of silence (Down states). The rhythmicity expressed during SWOs integrates neuronal and connectivity properties of the network and is often altered under pathological conditions. Adaptation mechanisms as well as synaptic inhibition mediated by GABA B receptors (GABA B -Rs) have been proposed as mechanisms governing the termination of Up states. The interplay between these two mechanisms is not well understood, and the role of GABA B -Rs controlling the whole cycle of the SWO has not been described. Here we contribute to its understanding by combining in vitro experiments on spontaneously active cortical slices and computational techniques. GABA B -R blockade modified the whole SWO cycle, not only elongating Up states, but also affecting the subsequent Down state duration. Furthermore, while adaptation tends to yield a rather regular behaviour, we demonstrate that GABA B -R activation desynchronizes the SWOs. Interestingly, variability changes could be accomplished in two different ways: by either shortening or lengthening the duration of Down states. Even when the most common observation following GABA B -Rs blocking is the lengthening of Down states, both changes are expressed experimentally and also in numerical simulations. Our simulations suggest that the sluggishness of GABA B -Rs to follow the excitatory fluctuations of the cortical network can explain these different network dynamics modulated by GABA B -Rs., (© 2020 The Authors. The Journal of Physiology © 2020 The Physiological Society.)

Case: A 29-year-old man was admitted with acute atraumatic left hip pain and inability to bear weight. Subsequent workup revealed an intracapsular pathologic fracture of the femoral neck secondary to a high-grade spindle cell sarcoma. A unique method of extra-articular resection and reconstruction using a 3-dimensional (3D)-printed custom cutting jig and a custom acetabular component was pursued. Wide margins were achieved without violating the joint capsule but preserving pelvic integrity, allowing a return to an active lifestyle., Conclusion: Three-dimensional-printed custom resection guides and implants can help achieve adequate resection margins while preserving pelvic integrity and function.

Some viruses encode inhibitory factors of apoptosis during infection to prolong cell viability and then to achieve a higher production of viral progeny or facilitate persistent infections. There is evidence that some gammaherpesviruses, including BoHV-4, carry genes that can both inhibit or induce apoptosis. BoHV-4 possesses two genes (ORF16 and ORF71) that code for proteins with anti-apoptotic functions, such as v-Bcl2 and v-Flip, respectively. Thus, it is relevant to study BoHV-4 in relation to the modulation of apoptosis in infected cells as a strategy for persistence in the host. The objective of this work was to analyze whether variations in v-Flip and v- Bcl2 of six phylogenetically divergent Argentinean isolates of BoHV-4 can influence the capacity of these strains to induce apoptosis in cell cultures. In this study, variations were mainly detected in the v-Flip gene and protein of the BoHV-4 strains belonging to genotype 3. Thus, it is possible to infer that sequence variations could be associated with some BoHV-4 genotype. Induction of apoptosis was not a significant event for any of the genetically distinct local isolates of BoHV-4 and there was not an evident relationship between the variability of both genes with the apoptotic effect of the phylogenetically distinct strains., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest with respect to the research, authorship, publication of this article and/or financial or personal relationships that could inappropriately influence this work., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Although periprosthetic joint infection (PJI) can affect multiple joints concurrently, the majority of patients with multiple prosthetic joints present with PJI of a single joint. Data regarding the optimal management of these patients are limited. We aimed to identify the prevalence, risk factors for a subsequent PJI, and clinical circumstances of PJI in patients with multiple prosthetic joints., Methods: We retrospectively reviewed the clinical records of 197 patients with ≥2 total joint prostheses in place who presented with PJI from 2000 to 2017. The average follow-up was 3.6 years (range, 0.5 to 17 years). Demographic data and risk factors for synchronous or metachronous PJI were identified. The time from the initial to the second PJI and organism profile data were collected as well. The workup for other joints with a prosthesis in place at the time of the initial PJI was noted., Results: Among the 197 patients with PJI and multiple joint prostheses in situ, 37 (19%) developed PJI in another joint; 11 had a synchronous PJI and 26 had a metachronous PJI. The average time between the first and the second infection in the metachronous cases was 848 days (range, 20 to 3,656 days). Females and patients with an initial PJI with methicillin-resistant Staphylococcus aureus (MRSA) were more likely to have a metachronous PJI, and patients with rheumatoid arthritis had an increased risk of a second (metachronous or synchronous) PJI. Three of 11 patients in the synchronous group and 19% (5) of the 26 in the metachronous group had bacteremia at the time of the initial PJI compared with 12% (19) of the 160 with a single PJI. The percentage of negative cultures increased from 10% for the initial PJIs to 38% for the metachronous PJIs., Conclusions: Patients who have multiple prosthetic joints in place and present with PJI of a single joint are at risk of developing PJI in another joint. Female sex, rheumatoid arthritis, bacteremia at presentation, and infection with MRSA appear to be risk factors for PJI of another joint. Clinical evaluation of the other prosthetic joint(s) should be carried out in all patients and aspiration of those joint(s) should be considered for patients with any of the above risk factors., Level of Evidence: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Bovine herpevsirus 4 (BoHV-4) is a gammaherpesvirus that has been associated with different clinical conditions in cattle. In Argentina, BoHV-4 was detected in diverse bovine samples. The aim of this study was to analyze the genetic relationship of 48 field BoHV-4 strains isolated from cattle in Argentina. According to thymidine kinase (tk) gene sequences, BoHV-4 isolates belong to genotypes 1, 2 and 3. Phylogenetic analyses confirmed the presence of the three previously described viral genotypes. However, some of the studied isolates presented conflicting phylogenetic signals between the studied markers. This suggests a complex evolutionary background, that is a history of recombination, incomplete lineage sorting (deep coalescence) or a combination of these, which requires further study. These potential events make difficult the diagnosis of BoHV-4 from clinical samples of cattle and may pose a significant problem for the control of the virus in the herds.

Introduction : Periprosthetic joint infection (PJI) remains one of the most dreaded and challenging complications in adult reconstruction. While primary total joint arthroplasty is one of the most successful surgeries in medicine, revisions secondary to infections do not hold as well. As the number of primary procedures increases, so will infections. In North America, two-stage exchange arthroplasty is the standard of care for patients with PJI, especially when the presentation is greater than 4 weeks after the index procedure. However, it is not necessarily the best option for all patients, particularly when compared to one-stage arthroplasty. Areas covered : The aim of this review is to analyze the indications, safety, and efficacy of two-stage exchange arthroplasty for the treatment of PJI and to compare the results reported 10 years ago with the ones of recent publications and those of one-stage arthroplasty. Expert opinion : Two-stage exchange arthroplasty is a safe and efficacious treatment particularly suited for recalcitrant infections, resistant organisms, and patients with certain host factors that make it more difficult to eradicate infection. However, one-stage arthroplasty might be well suited as well for infections caused by susceptible organisms and patients with minimal or no comorbidities or those unable to undergo two surgeries.

SuperCam is a highly integrated remote-sensing instrumental suite for NASA's Mars 2020 mission. It consists of a co-aligned combination of Laser-Induced Breakdown Spectroscopy (LIBS), Time-Resolved Raman and Luminescence (TRR/L), Visible and Infrared Spectroscopy (VISIR), together with sound recording (MIC) and high-magnification imaging techniques (RMI). They provide information on the mineralogy, geochemistry and mineral context around the Perseverance Rover. The calibration of this complex suite is a major challenge. Not only does each technique require its own standards or references, their combination also introduces new requirements to obtain optimal scientific output. Elemental composition, molecular vibrational features, fluorescence, morphology and texture provide a full picture of the sample with spectral information that needs to be co-aligned, correlated, and individually calibrated. The resulting hardware includes different kinds of targets, each one covering different needs of the instrument. Standards for imaging calibration, geological samples for mineral identification and chemometric calculations or spectral references to calibrate and evaluate the health of the instrument, are all included in the SuperCam Calibration Target (SCCT). The system also includes a specifically designed assembly in which the samples are mounted. This hardware allows the targets to survive the harsh environmental conditions of the launch, cruise, landing and operation on Mars during the whole mission. Here we summarize the design, development, integration, verification and functional testing of the SCCT. This work includes some key results obtained to verify the scientific outcome of the SuperCam system., Competing Interests: Conflicts of interest/Competing interestsThe authors declare that there are no conflicts of interest or competing interests., (© The Author(s) 2020.)

Background and Objectives: Atypical hemolytic uremic syndrome is a form of thrombotic microangiopathy caused by dysregulation of the alternative complement pathway. There is evidence showing complement activation in other thrombotic microangiopathies. The aim of this study was to evaluate complement activation in different thrombotic microangiopathies and to monitor treatment response., Design, Setting, Participants, & Measurements: Complement activation was assessed by exposing endothelial cells to sera or activated-patient plasma-citrated plasma mixed with a control sera pool (1:1)-to analyze C5b-9 deposits by immunofluorescence. Patients with atypical hemolytic uremic syndrome ( n =34) at different stages of the disease, HELLP syndrome (a pregnancy complication characterized by hemolysis, elevated liver enzymes, and low platelet count) or severe preeclampsia ( n =10), and malignant hypertension ( n =5) were included., Results: Acute phase atypical hemolytic uremic syndrome-activated plasma induced an increased C5b-9 deposition on endothelial cells. Standard and lower doses of eculizumab inhibited C5b-9 deposition in all patients with atypical hemolytic uremic syndrome, except in two who showed partial remission and clinical relapse. Significant fibrin formation was observed together with C5b-9 deposition. Results obtained using activated-plasma samples were more marked and reproducible than those obtained with sera. C5b-9 deposition was also increased with samples from patients with HELLP (all cases) and preeclampsia (90%) at disease onset. This increase was sustained in those with HELLP after 40 days, and levels normalized in patients with both HELLP and preeclampsia after 6-9 months. Complement activation in those with malignant hypertension was at control levels., Conclusions: The proposed methodology identifies complement overactivation in patients with atypical hemolytic uremic syndrome at acute phase and in other diseases such as HELLP syndrome and preeclampsia. Moreover, it is sensitive enough to individually assess the efficiency of the C5 inhibition treatment., (Copyright © 2019 by the American Society of Nephrology.)

Background: Although the factors associated to bacterial resistance in patients with asymptomatic bacteriuria (ASB) have been studied in pregnant, fertile age women, patients with spinal cord injury, and those with urogynecological disorders, nothing is known about the factors associated with multidrug-resistant (MDR) bacteria in patients with ASB and planned urological procedures. This study therefore sought to identify the sociodemographic and clinical factors associated with MDR bacteria in a cohort of patients with ASB scheduled for urological procedures., Methods: We conducted a nested case-control study on a cohort of patients with ASB and planned urological procedures at 3 Colombian medical centers. Cases were patients with MDR bacteria and controls were patients without MDR bacteria., Results: A total of 184 patients were included, 41.8% (n = 77) of whom presented ASB with MDR bacteria. The factors linking ASB with MDR bacteria were: advanced age (odds ratio, 1.03; 95% confidence interval, 1.01-1.06) and hospitalization within the 3-month period before surgery (odds ratio, 2.35; 95% confidence interval, 1.08-5.21)., Conclusions: Bacterial resistance is frequent among patients with ASB and planned urological procedures. Advanced age and prior hospitalization should be borne in mind for patients with planned urological procedures because they are factors associated with the presence of MDR bacteria., (Copyright © 2019 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Many surgeons add topical antibiotics to irrigation solutions assuming that this has a local effect and eliminates bacteria. However, prior studies have suggested that the addition of antibiotics to irrigation solution confers little benefit, adds cost, may potentiate anaphylactic reactions, and may contribute to antimicrobial resistance. We sought to compare the antimicrobial efficacy and cytotoxicity of an irrigation solution containing polymyxin-bacitracin with other commonly used irrigation solutions., Methods: Staphylococcus aureus and Escherichia coli were exposed to irrigation solutions containing topical antibiotics (500,000-U/L polymyxin and 50,000-U/L bacitracin; 1-g/L vancomycin; or 80-mg/L gentamicin), as well as commonly used irrigation solutions (saline solution 0.9%; povidone-iodine 0.3%; chlorhexidine 0.05%; Castile soap 0.45%; and sodium hypochlorite 0.125%). Following 1 and 3 minutes of exposure, surviving bacteria were manually counted. Failure to eradicate all bacteria in any of the 3 replicates was considered not effective for that respective solution. Cytotoxicity analysis in human fibroblasts, osteoblasts, and chondrocytes exposed to the irrigation solutions was performed by visualization of cell structure and was quantified by lactate dehydrogenase (LDH) activity. Efficacy and cytotoxicity were assessed in triplicate experiments, with generalized linear mixed models., Results: Polymyxin-bacitracin, saline solution, and Castile soap at both exposure times were not effective at eradicating S. aureus or E. coli. In contrast, povidone-iodine, chlorhexidine, and sodium hypochlorite irrigation were effective against both S. aureus and E. coli (p < 0.001). Vancomycin irrigation was effective against S. aureus but not against E. coli, whereas gentamicin irrigation showed partial efficacy against E. coli but none against S. aureus. Within fibroblasts, the greatest cytotoxicity was seen with chlorhexidine (mean [and standard error], 49.38% ± 0.80%; p < 0.0001), followed by Castile soap (33.57% ± 2.17%; p < 0.0001) and polymyxin-bacitracin (8.90% ± 1.40%). Povidone-iodine showed the least cytotoxicity of the efficacious solutions (5.00% ± 0.86%). Similar trends were seen at both exposure times and across fibroblasts, osteoblasts, and chondrocytes., Conclusions: Irrigation with polymyxin-bacitracin was ineffective at bacterial eradication, and statistically inferior to povidone-iodine. Chlorhexidine lavage conferred the greatest in vitro cytotoxicity., Clinical Relevance: These data suggest that the addition of polymyxin-bacitracin to saline solution irrigation has little value. Given the cost and antimicrobial resistance implications, our findings, combined with prior clinical literature, provide adequate reason to avoid widespread use of antibiotics in irrigation solutions. Povidone-iodine may be a more effective and safer option.

In this work we model the glomerular filtration barrier, the structure responsible for filtering the blood and preventing the loss of proteins, using human podocytes and glomerular endothelial cells seeded into microfluidic chips. In long-term cultures, cells maintain their morphology, form capillary-like structures and express slit diaphragm proteins. This system recapitulates functions and structure of the glomerulus, including permselectivity. When exposed to sera from patients with anti-podocyte autoantibodies, the chips show albuminuria proportional to patients' proteinuria, phenomenon not observed with sera from healthy controls or individuals with primary podocyte defects. We also show its applicability for renal disease modeling and drug testing. A total of 2000 independent chips were analyzed, supporting high reproducibility and validation of the system for high-throughput screening of therapeutic compounds. The study of the patho-physiology of the glomerulus and identification of therapeutic targets are also feasible using this chip.

Background: Direct anterior approach (DAA) total hip arthroplasty can be performed through a traditional vertical incision or a horizontal (bikini) incision. The purpose of this study is to compare the 2 approaches, performed by a single surgeon past the learning curve, in terms of (1) overall wound complications and (2) patient-reported esthetics at the 6-month follow-up., Methods: A case-control retrospective study was conducted. Eighty-six bikini DAA patients were matched 3:1 to 230 conventional DAA patients for gender, age, body mass index (BMI), and American Society of Anesthesiologists score. Outcomes evaluated included wound complications, acute periprosthetic joint infection, transfusion, length of surgery, and dysesthesia. A subgroup analysis was also performed on obese patients, BMI greater than 30 kg/m 2 . Furthermore, the patients rated cosmesis of the incision at 6 months using a Patient Scar Assessment Scale and the Vancouver Scar Assessment Scale., Results: Bikini patients had lower rates of delayed wound healing compared to conventional incision (2.3% vs 6.1%, P = .087). This difference was statistically significant (0% vs 16.6%, P < .05) in obese patients. There was no difference in terms of incision cosmesis between the 2 incision types., Conclusion: Our study demonstrates that the DAA total hip arthroplasty can be performed safely through an alternative horizontal bikini incision with complication rates equivalent to conventional incision DAA and to those in other approaches when performed by surgeons in a high volume, efficient hip replacement institution. In patients whose BMI is >30, a potential benefit of the horizontal incision may be lower wound complications. This study design should be performed at other institutions and ideally at a multi-institution level to evaluate if results can be corroborated. Our opinion is that the horizontal bikini incision should be utilized but only after mastery of the DAA approach using the conventional vertical incision., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Total knee arthroplasty (TKA) is a highly successful operation that improves patients' quality of life and functionality. Yet, up to 20% of TKA patients remain unsatisfied with their clinical result. Robotic TKA has gained increased attention and popularity as a means of improving patient satisfaction. The promise of robotic-assisted TKA is that it provides a surgeon with a tool that accurately executes bone cuts according to presurgical planning, as well as provides the surgeon with intraoperative feedback helpful for restoring knee kinematics and soft tissue balance. Several systems are now available, each with their own advantages and disadvantages. Evidence that the use of robotics will lead to improved implant survival, function, and patient-reported outcomes is slowly being accumulated, but this has not been clearly proven to date. Recent literature does show that the use of robotics during TKA is not associated with increased surgical time or complications. The goal of this review is to provide an objective assessment of the evidence surrounding robotic technology for TKA., Competing Interests: Dr. Hozack reports grants and personal fees from Stryker, other from JOA, outside the submitted work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Following total knee arthroplasty and total hip arthroplasty, wound-related problems and deep periprosthetic joint infection may present in a similar fashion. Irrigation and debridement (I&D) has a great role in management of patients with early infection. The question that often arises is how to tell the difference between superficial and deep infection. This study evaluated the role and outcomes of both superficial and deep I&D in patients with wound-related issues and/or suspected periprosthetic joint infection., Methods: A retrospective study was conducted evaluating patients who underwent I&D within 28 days of total joint arthroplasty. A total of 176 cases with a minimum of 1-year follow-up were identified, and clinical records were reviewed in detail. Reoperations included superficial (fascia not opened) or deep (fascia opened) I&D. Failure was defined as the need for further surgical intervention within 1 year of initial I&D., Results: The overall success for superficial I&D was 84.28% vs 68.86% for deep I&D. The success of both deep and superficial I&D was higher if the I&D was performed closer to the index surgery. Superficial I&D in patients with a positive joint aspiration or evidence of intraoperative purulence or those in whom had no subcutaneous fluid had higher failure rates., Conclusion: Superficial I&D is a viable option in patients with wound-related issues as long as joint aspiration is performed to rule out infection involving the prosthesis. If there are findings of no fluid or purulence, fascia may need to be opened and the deeper tissues explored., (Copyright © 2019 Elsevier Inc. All rights reserved.)